32p-sodium orto-phosphate for injection.

Instructions for use

NAME OF THE MEDICINAL PRODUCT: 32P-Sodium orto-phosphate for injection. 2. QUALITATIVE AND QUANTITITATIVE COMPOSITION:
32P Acidum phosphoricum 74 -370 MBq (2 - 10 mCi) or
Phosphorus in the form of sodium phosphate
The product does not contain any antimicrobial additives.
3. PHARMACEUTICAL FORM: Radiopharamceuticals - solution for injection. 4. CLINICAL PARTICULARS 4.1. Indication Therapy of polycythemia vera and polythrombocytemia and related disorders, leukemia and other neoplastic haematological disorders. Palliative treatment of painful bone metastasis from prostate, breast, lung and other carcinomas is reported but its myelotoxicity should be considered. 4.2.Posology and method of administration The preparation is destined for direct oral or intravenous administration to the patient in aliquots varying in activity depending on therapeutic application. 4.2.1. In the treatment of polycythemia vera recommended dose is 74 - 111 MBq (2 - 3 mCi) on 1 m2 of body surface but not more than 185 MBq (5 mCi), another method recommends first application of 111 MBq (3 mCi) and if after 3 months the symptoms of polycythemia are still present the second, higher of 25% dose is administered. Single dose should not be higher than 250 MBq (7 mCi). In leukemia approximately 37 -74 MBq (1 to 2 mCi) is given weekly until the white blood cell count is sufficiently decreased. 4.2.2. In the treatment of of bone metastases the doses of 370 do 555 MBq (10 - 15 mCi) can be administered for pain palliation in terminally ill patients who have not responded to conventional therapies (hormones, wide or narrow beam radiotherpay, cytotoxicosis etc.) who present with widespread painful bone matestases from assorted primaries and who may be requiring or are likely to require increasing quantities of strong analgesics. Reduction of bone pain may take several weeks to occur and may be associated with improved morale as well as decreased analgesic requirements. 4.3. Contra indications This agent is contraindicated in children, during pregnancy or females wishing to continue breast feeding. If the patients platelet count is less than 15,000 it is suggested not to administer the preparation. 4.4. Special precautions
The administration of 32P is usually not recommended in patients under 50 years of age. It should be noted that polycythemia rubra vera may also be palliated by repeated venesections, thioureas or regular courses of oral chlorambucil. More appropriate radiopharmaceuticals may be available for the treatment of painful bone metastases secondary to prostatic cancer. Because of the relatively long effective half life 32P-Sodium orto-phosphate it should not be administered to patients with a very short life expectancy. Radiopharmaceutical agents should be used only by qualified personnel with the appropriate government authorisation for the use and manipulation of radionuclides. This radiopharmaceutical may be received, used and administered only by authorised personnel in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licenses of the local competent official organisations. Because of the risk of serious, delayed bone marrow depression, cytotoxic agents should not be prescribed until aperiod of four months has elapsed from treatment with 32P. 4.5. Interactions The use of oestrogen and androgen preparations may affect the metabolism and retention of labelled phosphorus 32P. Interactions with other drugs are not known; with respect to the adverse effect on bone marrow, the product should not be administered simultaneously with chemotherapy and radiation therapy (or within a short interval after them), if the therapeutic effect does not outbalance the risk. 4.6. Pregnancy and lactation When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. Breast feeding should be discontinued after administration because of the potential hazard to the suckling; breast -feeding can only be restarted when the radiation dose obtained by the child due to the consuming of this milk and contact with the mother is lower than limits given by regulations on ionising radiation protection. Pregnancy: There are no available data in animals or man but, at the activities proposed, this radiopharmaceutical is likely to both mutagenic and teratogenic. The administration of 32P is therefore contraindicated in pregnancy. Where uncertainty exists it is important that radiation exposure should be the minimum consistent with achieving the desired clinical information. Alternative techniques which do not involve ionising radiation should always be considered. 4.7. Effects on ability to drive and use machines The product is safe. 4.8. Undesirable effects Therapy with 32P-Sodium orto-phosphate inj. gives the risk of leukemia in 2 - 15% of patients during 10 years (similar to chemotherapy). 4.9. Overdose
32P-Sodium orto-phosphate should be administered by qualified personnel in designated clinical settings. The preparation is delivered in portions prepared on request with a patient activity dose. The possibility of overdosing is therefore markedly reduced. In the event of this occuring, however, overdose would be limited to excessive body irradiation rather than the remote possibility of chemical overdose. Excessive radiation effects all rapidly developing dividing tissues but those on haemopoietic tissues could be delayed for several months. In the event of overdosage an appropriate increase in fluid intake is advised to promote diuresis and excretion of the label (forced diuresis). Frequent bladder emptying is also advised. In addition, the administration of unlabelled phosphate salts can reduce the incorporation of the radionuclide in body tissues thereby reducing exposure. 5. PHARMACOLOGICAL PROPERTIES 5.1., 5.2. Pharmacodynamic and pharmacokinetic properties Polycythemia vera is a disease characterized by an increased red blood cell mass, frequently associated with bone marrow hyperactivity. Therapy results from radiation injury to the cell precursors and the bone marrow due to bone accumulation of 32P. A fraction of 0.30 of intravenously administered activity is assumed to go to mineral bone and to be permanently retained, and 0.70 is assumed to be distributed in soft tissues.
After injection the soluble radiophosphate is concentrated by rapidly proliferating tissue. The blood cells precursors in the bone marrow divide and proliferate rapidly in health and even more so in these diseases. The radionuclide 32P present in sodium ortophosphate-32P selectively concentrates in the mitotically active cells of the bone marrow and in trabecular and cortical bone. Selective uptake of 32P by haemopoietic tissue provides a continuous irradiation of dividing cells which significantly interferes with their viability. Its uptake by the different tissues depends on several factors including exchangeable tissue phosphate in the tissue, the rate of new tissue formation and tissue vascularity.
5.3. Preclinical safety data 32P-Sodium orto-phosphate has not been subjected to acute toxicity studies in any animal species. Likewise, its carcinogenicity or reproductive toxicity have not been evaluated. 5.4. Radiation dosimetry Phosphorus [32P] is a beta emitter (Emax 1.71 MeV) with a physical half-life of 14.29 days. It gives off Bremsstrahlung. According to ICRP model, a fraction of 0.30 of intravenously administered activity is assumed to go to mineral bone and to be permanently retained, and 0.70 is assumed to be distributed in soft tissues. Phosphorus metabolism is complex. Activity deposited in soft tissues is assumed to be rapidly eliminated from the body (30%) and about 40% of activity possesses a 19-day biological half-life, the remaining 30% is reduced by radioactive decay. The high-energy beta emissions can present a substantial skin dose hazard. The effective dose equivalent at adult patient (70 kg) after administration of 32P-Sodium orto-phosphate is 2.20 mSv/MBq.The radiation dose absorbed in breast is about 0.92 mGy/MBq, in the bone marrow 11.0 mGy/MBq and in bone surfaces about 11.0 mGy/MBq. In the other organs, the absorbed radiation doses are lower (0.74 mGy/MBq). The radiation dose to patients from the administered with 32P-Sodium orto-phosphate inj. located in different organs and tissues. This distribution is presented in the ICRP 53: Annals of the ICRP, Radiation dose to Patients from Radiopharmaceuticals. Vol.18 No. 1-4 1987 p.83-84.
Absorber dose per unit activity administrered (mGy/MBq)